DESCRIPTION (As Adapted From the Investigator's Abstract): The Specific Aims are: Specific Aim 1 is designed to test the hypothesis that constitutive activation of PI3 kinase and its downstream signaling pathways mediate the alter phenotypes expressed by transformed HME cells expressing varying levels of erbB-2. Specific Aim 2 will be used to determine the mechanisms by which other oncogenes, that are amplified and/or overexpressed in human breast cancer cells, transform HME cells. This will be done by examining, in the context of the model recently developed, the ability of specific known and candidate oncogenes to induce phenotypes that are induced by erbB-2, when overexpressed to levels similar to that of breast cancer cell lines. The phenotypes to be studied include; factor independent survival/proliferation, growth in soft agar, and invasion of basement membranes. Specific Aim 3 is designed to examine the epigenetic consequences of overexpression of erbB-2 and other putative breast cancer oncogenes in order to identify common transcriptional events mediated by these genes, and to determine their role in the acquisition of specific altered phenotypes.